On July 24, 2020, Hendricks pitched a complete game shutout in the Cubs' season opener versus the Brewers, only throwing 103 pitches with 3 hits allowed, 9 strikeouts, and no walks. It was the first Opening Day shutout by a Cubs pitcher since Bill Bonham in 1974, and the first Opening Day shutout in MLB since Clayton Kershaw in 2013.
In 2020 he was 6-5 with a 2.88 ERA. He led the NL in fewest walks per 9 IP (0.885), and in strikeout/walk ratio (8.000), and was 8th in losses.